Sensor for biomolecules

ABSTRACT

A method for sensing biomolecules in an electrolyte includes exposing a gate dielectric surface of a sensor comprising a silicon fin to the electrolyte, wherein the gate dielectric surface comprises a dielectric material and antibodies configured to bind with the biomolecules; applying a gate voltage to an electrode immersed in the electrolyte; and measuring a change in a drain current flowing in the silicon fin; and determining an amount of the biomolecules that are present in the electrolyte based on the change in the drain current.

CROSS REFERENCE TO RELATED APPLICATION

This application is a divisional of U.S. application Ser. No. 12/537,063filed on Aug. 6, 2009, the disclosure of which is incorporated byreference herein in its entirety.

FIELD OF INVENTION

This disclosure relates generally to the field of sensors forbiomolecule detection.

DESCRIPTION OF RELATED ART

Biomolecules, which may include proteins or viruses, play an importantrole in many illnesses; the study of biomolecules is essential forimproved, cost effective disease diagnosis and treatment. Some methodsthat may be used to detect biomolecules include fluorescence orradioactive labeling, and patch clamp. However, these methods may belabor intensive, costly, or have limited sensitivity. Such detectionmethods may also be difficult to integrate into systems that includeadditional functionality such as sample delivery, data acquisition, ordata transmission. For example, the patch clamp method is used forsensing proteins such as ion channels that are embedded in the membraneof a cell. This method includes a pipette that punctures the cellmembrane embedded with proteins. Due to the presence of the pipette, thepatch clamp method has limited scope for miniaturization or integrationonto a multifunctional platform.

A field effect transistor (FET) based sensor, such as large area planarFET or a back-gated silicon nanowire FET, may be used to detectbiomolecules by measuring the drain current in the sub-threshold regimewhere the drain current has an exponential dependence on the gatevoltage of the FET. A large area planar FET may have limitedsensitivity, and may therefore detect only high concentrations ofbiomolecules. A back-gated silicon nanowire FET exhibits improvedsensitivity in comparison to large area planar FET based sensors. In aback-gated silicon nanowire FET, silicon nanowire forms the sensingsurface, buried oxide act as the gate dielectric and silicon substrateact as the gate. The sensitivity of a back-gated nanowire FET may bedegraded due to two factors: a large sub-threshold slope due to thethick buried oxide that acts as the gate dielectric, and formation ofthe inversion layer at the silicon/oxide interface such that is locatedaway from the sensing surface of the silicon channel. Since thesefactors are inherent structural features of a back-gated siliconnanowire FET, its sensitivity can only enhanced by reducing the siliconnanowire thickness. However, reduction in silicon nanowire thicknesscauses the sensing area to decrease, resulting in slower response times,and also making the wires relatively fragile. In summary, back-gatedsilicon nanowire FET sensors have an inherent structural designdisadvantage for biomolecule sensing applications.

SUMMARY

In one aspect, a method for sensing biomolecules in an electrolyteincludes exposing a gate dielectric surface of a sensor comprising asilicon fin to the electrolyte, wherein the gate dielectric surfacecomprises a dielectric material and antibodies configured to bind withthe biomolecules; applying a gate voltage to an electrode immersed inthe electrolyte; and measuring a change in a drain current flowing inthe silicon fin; and determining an amount of the biomolecules that arepresent in the electrolyte based on the change in the drain current.

Additional features are realized through the techniques of the presentexemplary embodiment. Other embodiments are described in detail hereinand are considered a part of what is claimed. For a better understandingof the features of the exemplary embodiment, refer to the descriptionand to the drawings.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

Referring now to the drawings wherein like elements are numbered alikein the several FIGURES:

FIG. 1 illustrates a cross section of an embodiment of a fin FET basedsensor for biomolecules.

FIG. 2 illustrates a top view of an embodiment of a fin FET based sensorfor biomolecules.

FIG. 3 illustrates a cross section of an embodiment of a sensor forbiomolecules comprising multiple fin FETs.

FIG. 4 illustrates a top view of an embodiment of a sensor forbiomolecules comprising multiple fin FETs.

FIG. 5 illustrates a cross-section of an embodiment of a sensor forbiomolecules comprising multiple fin FETS.

FIG. 6 illustrates a cross-section of an embodiment of a sensor forbiomolecules comprising fin and planar FETs.

FIG. 7A illustrates a cross-section of the sensor for biomoleculescomprising a planar FET that is located between two adjacent fin FETs.

FIG. 7B illustrates a top view of the sensor for biomolecules comprisinga planar FET that is located between two adjacent fin FETs.

FIG. 8 illustrates a cross-section of an embodiment of a sensor forbiomolecules embedded in a membrane.

FIG. 9 illustrates an embodiment of a method for detection ofbiomolecules in an electrolyte using a sensor.

FIG. 10 illustrates an embodiment of a method for detection ofbiomolecules in a membrane using a sensor.

DETAILED DESCRIPTION

Embodiments of systems and methods for a sensor for biomolecules areprovided, with exemplary embodiments being discussed below in detail. Astructure for FET based sensor is proposed which overcomes the drawbacksof back-gated silicon nanowire FET sensor as described in above.Consequently, the proposed sensor structure may have significantlyimproved sensitivity, larger sensing area and higher yield in comparisonto a back-gated silicon nanowire FET.

A sensor for biomolecules, which may include, but are not limited to,proteins or viruses, may comprise a FET-type structure comprising one ormore silicon fins The silicon fin structure may have a low sub-thresholdslope (SS), an inversion layer formed close to the sensing surface, andvolume inversion effects, which may act to increase the sensitivity ofthe sensor. Response time of the sensor may also be reduced. The sensorstructure may be fabricated using standard silicon process technology,allowing the sensor to be cost effectively mass produced and easilyintegrated into a multi-function silicon chip that performs suchfunctions as sample delivery, data acquisition, or data transmission.

A FET-based sensor may detect biomolecules by measuring the draincurrent (I_(d)) of the FET structure in the sub-threshold regime, whereI_(d) has exponential dependence on a gate voltage. The majority ofbiomolecules are charged, therefore, when a charged biomolecule is inthe vicinity of a silicon channel of the FET structure, the biomoleculemay cause the drain current to change by ΔI_(d), whereΔI _(d) =μ*C _(ox) /SS,where C_(ox) is the gate oxide capacitance, μ is the mobility ofelectrons or holes in the silicon channel, and SS is the sub-thresholdslope. Since ΔI_(d) is a measure of sensor sensitivity, the sensitivitymay be maximized by utilization of a FET structure that has a relativelysmall sub-threshold slope and relatively large C_(ox) and μ values.

The silicon fin width and height may be adjusted so as to obtain a SS ofabout 62 mV/decade. Response time of the sensor may also be reduced byincreasing the surface area of a silicon fin. A reduction in responsetime without degradation of sensitivity may be obtained by a channellength (L_(g)) of a silicon fin that is greater than about 0.5 micron(μm), a silicon fin width (W_(si)) that is less than about 30 nanometers(nm), and a silicon fin height (H_(si)) that is greater than or equal totwice W_(si). A W_(si) of less than about 25 nm may result in a volumeinversion effect, which may cause mobility (μ) to increase. The gatedielectric may comprise a layer of SiO2 or SiON, or a stack consistingof SiON and metal oxide insulator such as HfO2, with an equivalent oxidethickness of about 5 nm. An electrolyte may act as the top FET gate. Thegate dielectric may be covered with antibodies that selectively bindwith the biomolecules to be detected in some embodiments.

FIG. 1 illustrates a cross-section of an embodiment of a fin FET basedsensor 100 for biomolecules. Silicon fin 101 comprises undoped silicon.Silicon fin 101 is coated with gate dielectric 102. Gate dielectriclayer 102 forms the biomolecule detection surface, and may compriseoxide/HfO2 stack or SiON in some embodiments. The gate dielectric layer102 further comprises antibodies that selectively bind with thebiomolecules to be detected in some embodiments. Buried oxide layer 103and silicon back gate 104 form a base of the sensor 100. Line 105illustrates the silicon fin height (H_(si)), and line 106 illustratesthe silicon fin width (W_(si)).

FIG. 2 illustrates a top view of an embodiment of a fin FET based sensor200 for biomolecules. Silicon fin 201 comprises a channel of undopedsilicon, and has a channel length (L_(g)) illustrated by line 208. Gatedielectric layers 202 and 203 form the biomolecule detection surface,and comprise oxide/HfO2 stack or SiON in some embodiments. The gatedielectric layers 202 and 203 further comprise antibodies thatselectively bind with the biomolecules to be detected in someembodiments. Drain 204 comprises heavily doped n+ or p+ silicon, andsource 205 comprises heavily doped silicon of the same doping type asthe drain. Regions 206 and 207 comprise thick oxide layers that act toisolate the drain 204 and source 205 from an electrolyte containingbiomolecules that covers the gate dielectric layers 202 and 203 inoperation.

Some embodiments may comprise multiple fin FETs, which reduce theresponse time of the sensor by increasing the detection surface area.FIG. 3 illustrates an embodiment of a cross-section of a sensor 300 forbiomolecules comprising multiple fin FETs. Silicon fins 301, 303, and305 comprise undoped silicon. Silicon fins 301, 303, and 305 are coatedwith gate dielectric layers 302, 304, and 306. Gate dielectric layers302, 304, and 306 form the biomolecule detection surface, and maycomprise oxide/HfO2 stack or SiON in some embodiments. The gatedielectric layers 302, 304, and 306 further comprise antibodies thatselectively bind with the biomolecules to be detected in someembodiments. Buried oxide layer 307 and silicon back gate 308 form thebase of the sensor 300. Line 309 illustrates the silicon fin height(H_(si)), line 310 illustrates the silicon fin width (W_(si)), and line311 illustrates the spacing between fins. Three fin FETs are shown inthe embodiment of FIG. 3 for illustrative purposes only; any appropriatenumber of fin FETs may comprise a sensor for biomolecules.

FIG. 4 illustrates a top view of an embodiment of a sensor 400 forbiomolecules comprising multiple fin FETs. Silicon fins 401, 404, and407 comprise channels of undoped silicon having a channel length (L_(g))illustrated by line 414. Gate dielectric layers 402, 403, 405, 406, 408,and 409 form the biomolecule detection surface, and comprise oxide/HfO2stack or SiON in some embodiments. The gate dielectric layers 402, 403,405, 406, 408, and 409 further comprise antibodies that selectively bindwith the biomolecules to be detected in some embodiments. Drain 410comprises heavily doped n+or p+silicon, and source 411 comprises heavilydoped silicon of the same doping type as the drain. Regions 412 and 413comprise thick oxide layers that act to isolate the drain 410 and source411 from an electrolyte containing biomolecules that covers the gatedielectric layers 402, 403, 405, 406, 408, and 409 in operation. Threefin FETs with common source and drain regions 410 and 411 are shown inthe embodiment of FIG. 4 for illustrative purposes only; any appropriatenumber of fin FETs may comprise a sensor for biomolecules.

FIG. 5 illustrates a cross-section of an embodiment of a sensor 500 forbiomolecules comprising multiple fin FETs that is immersed in anelectrolyte solution 510 comprising biomolecules 509. Fins 501, 503, and505 are coated in gate dielectric 502, 504, and 506. Buried oxide layer507 and silicon back gate 508 form a base of sensor 500. Electrolytesolution 510 acts as the FET top gate. Biomolecules 509 bind withantibodies located on gate dielectric 502, 504, and 506, causing achange (ΔI_(d)) in the drain current (I_(d)) of the sensor 500, allowingthe biomolecules 509 to be detected. The gate voltage is supplied by anelectrode 511, which comprises a silver wire coated with silver chloridein some embodiments. The back gate 508 may have the same polarity biasas the electrolyte 510, or the back gate 508 may be grounded. Top gateelectrolyte 510 is in the sub-threshold regime. For the case of n-typesource and drain regions, a positive polarity voltage is applied at thedrain, the source voltage is held at 0V and a voltage betweenapproximately 100 mV and 3V is applied at electrode 511, causing a draincurrent to flow between the source and drain of the sensor (source anddrain are discussed above, see, for example, elements 204 and 250 ofFIG. 2, and elements 410 and 411 of FIG. 4). When biomolecules 509attaches to gate dielectric layers 502, 504, and 506, the drain currentchanges according to the charge of the biomolecules, allowing detectionof the biomolecules. Three fin FETs are shown in the embodiment of FIG.5 for illustrative purposes only; any appropriate number of fin FETs maycomprise a sensor for biomolecules.

A sensor structure may comprise a single fin FET or multiple fin FETswith common source and drain depending on whether sensitivity orresponse time is a more important for a particular biomolecule detectionapplication. If higher sensitivity is desired, a single fin FETstructure may be used, whereas multiple fin FETs reduce the responsetime. The spacing between the fin FETs in a multiple fin FET embodimentmay be adjusted so as to provide size selectivity for detectingbiomolecules. For example, for a sensor configured to detect a viruswith a diameter of approximately 100 nm, the spacing between fin FETsmay be made slightly (approximately 5%-20%) larger than the diameter ofthe virus to be detected. Any appropriate number of fin FETs maycomprise an embodiment of a sensor for biomolecules.

FIG. 6 illustrates a cross-sectional view of an embodiment of a sensor600 comprising fin and planar FETs. Planar FETs 609 and 610 compriseextremely thin planar silicon layers; planar FETs 609 and 610 arelocated between adjacent fin FETs 601 and 603, and 603 and 605,respectively. Line 613 illustrates the silicon fin FET height (H_(si)).Planar silicon FETs 609 and 610 comprise undoped silicon of a thicknessthat is less than H_(si), and may be less than 10 nm in someembodiments. The width of planar silicon FETs 609 and 610 is illustratedby line 614, which is of approximately the same width as the spacingbetween silicon fins 603 and 605. Planar silicon FETs 609 and 610 andfin FETs 601, 603, and 605 are coated with gate dielectric 602, 604,606, 611, and 612. Gate dielectric layers form the biomolecule detectionsurface, and comprise oxide/HfO2 stack or SiON in some embodiments. Thegate dielectric layers comprise antibodies that selectively bind withthe biomolecules to be detected in some embodiments. Buried oxide layer607 and silicon back gate 608 form a base of sensor 600. Three fin FETsand two planar FETs are shown in the embodiment of FIG. 6 forillustrative purposes only; any appropriate number of fin and planarFETs may comprise a sensor for biomolecules.

FIG. 7A illustrates a cross-sectional view 700 a of a sensor comprisinga planar FET, and FIG. 7B illustrates a top view 700 b of a sensorcomprising a planar FET. Referring to FIG. 7A, Gate dielectric layer 701covers planar silicon 702, which is disposed on buried oxide layer 703and back gate 704. Referring to FIG. 7B, source region 707 is located atone end of planar silicon 705, and drain region 706 is located at theopposite end of planar silicon 705. Drain 706 comprises heavily doped n+or p+ silicon, and source 707 comprises heavily doped silicon of thesame doping type as the drain. Source region 707 and drain region 706are insulated by thick oxide regions 708 and 709. Planar silicon 705 iscovered with a gate dielectric, and has a channel length L_(g)illustrated by line 710, which is approximately equal to the channellength of a silicon fin, as illustrated by element 208 of FIG. 2.

FIG. 8 illustrates a side view of an embodiment of a sensor 800configured to detect biomolecules in a membrane 811. Membrane 811 maycontain embedded biomolecules such as ion channel or ion pump proteins.Electrolyte 810 acts as the top FET gate. Fins 801, 803, and 805 arecoated in gate dielectric 802, 804, and 806. Buried oxide layer 807 andsilicon back gate 808 form a base of sensor 800. The gate voltage issupplied at electrode 809, which may comprise silver wire coated withsilver chloride in some embodiments. The back gate 808 may have the samepolarity bias as the membrane, or be grounded. Three fins are shown inthe embodiment of FIG. 8 for illustrative purposes only; any appropriatenumber of fins may comprise a sensor for biomolecules.

FIG. 9 illustrates an embodiment of a method 900 for detection ofbiomolecules using a sensor. In block 901, a gate dielectric surface ofa silicon fin is coated with antibodies that selectively bind a proteinor virus to be detected. In block 902, the gate dielectric surface isbrought into contact with an electrode dipped in an electrolyte. Theelectrolyte acts as a FET gate. In block 903, a voltage is applied atthe sensor drain, and the sensor source voltage is set to 0V. In block904, a gate voltage (V_(g)) is applied at the electrode. A voltage(V_(b)) may also be applied to the back gate for threshold voltagetuning in some embodiments. In block 905, the drain current I_(d) in theabsence of biomolecules is measured. In block 906, the biomolecules areadded to the electrolyte. In block 907, the biomolecules bind to theantibodies on the gate dielectric surface, thereby cause the draincurrent I_(d) in the sub-threshold regime of the sensor to change byΔI_(d), and the bio-molecules to be detected according to ΔI_(d).

FIG. 10 illustrates an embodiment of a method 1000 for detectingbiomolecules embedded in the membrane of a cell. In block 1001, the gatedielectric surface is brought into contact with an electrode dipped inan electrolyte. In block 1002, a membrane embedded with biomoleculessuch as ion channel proteins is brought into contact with the gatedielectric surface. In block 1003, a voltage is applied at the drain,and the source voltage is set to 0V. In block 1004, a gate voltage(V_(g)) is applied at the electrode. A voltage (V_(b)) may also beapplied to the back gate for threshold voltage tuning in someembodiments. In block 1005, the drain current I_(d) is measured. Inblock 1006, liagand molecules are added to the electrolyte; the liagandmolecules cause the pores in the ion channels of the membrane to open,causing ions to flow in or out of the cell, causing a localized changein ion density. In block 1007, the drain current I_(d) in thesub-threshold regime of the sensor is measured to determine the ΔI_(d)caused by the change in ion density caused by the opening of ion channelproteins. While the embodiment of FIG. 10 has been described withreference to liagand gated ion channel proteins, a similar procedure maybe used for voltage gated ion channel proteins or ion pump proteins.

The technical effects and benefits of exemplary embodiments includeproviding a biomolecule sensor with relatively low response time andhigh sensitivity. The sensor may be relatively cheap to manufacture, andeasy to integrate into a multi-functional silicon chip.

The terminology used herein is for the purpose of describing particularembodiments only and is not intended to be limiting of the invention. Asused herein, the singular forms “a”, “an”, and “the” are intended toinclude the plural forms as well, unless the context clearly indicatesotherwise. It will be further understood that the terms “comprises”and/or “comprising,” when used in this specification, specify thepresence of stated features, integers, steps, operations, elements,and/or components, but do not preclude the presence or addition of oneor more other features, integers, steps, operations, elements,components, and/or groups thereof.

The corresponding structures, materials, acts, and equivalents of allmeans or step plus function elements in the claims below are intended toinclude any structure, material, or act for performing the function incombination with other claimed elements as specifically claimed. Thedescription of the present invention has been presented for purposes ofillustration and description, but is not intended to be exhaustive orlimited to the invention in the form disclosed. Many modifications andvariations will be apparent to those of ordinary skill in the artwithout departing from the scope and spirit of the invention. Theembodiment was chosen and described in order to best explain theprinciples of the invention and the practical application, and to enableothers of ordinary skill in the art to understand the invention forvarious embodiments with various modifications as are suited to theparticular use contemplated. Specifically, while an n-type FET-sensorembodiment was chosen to explain the principles of the invention, theprinciples of the invention also apply to embodiments comprising p-typeFET-sensors.

The invention claimed is:
 1. A method for sensing biomolecules in anelectrolyte, the method comprising: exposing a gate dielectric surfaceof a sensor comprising a plurality of silicon fins to the electrolyte,wherein the gate dielectric surface comprises a dielectric material thatsubstantially covers an upper surface of the sensor and antibodiesconfigured to bind with the biomolecules; applying a gate voltage to anelectrode immersed in the electrolyte; and measuring a change in a draincurrent flowing in one or more of the plurality of the silicon fins; anddetermining an amount of the biomolecules that are present in theelectrolyte based on the change in the drain current; wherein the sensorcomprises a plurality of fin field effect transistors (finFETs), each ofthe plurality of silicon fins comprises a channel of each of theplurality of the finFETs and a planar field effect transistor (FET)located between two adjacent silicon fins, the planer FET having a widthapproximately equal to a distance separating the adjacent silicon fins,wherein the width of the planar FET is approximately 5% to 20% largerthan a diameter of the biomolecules to be sensed.
 2. The method of claim1, wherein the silicon fin has a width of less than about 25 nanometers(nm) and a height greater than or equal to about twice the width.
 3. Themethod of claim 1, wherein the silicon fin has a channel length ofgreater than about 0.5 microns (μm).
 4. The method of claim 1, whereinthe dielectric material that comprises the gate dielectric comprisesSiON/Hf0 ₂, and has a thickness of less than about 10 nm.
 5. The methodof claim 1, wherein the electrolyte comprises a gate of the finFET,wherein the electrolyte is separated from the silicon fin by thedielectric material of the gate dielectric.
 6. The method of claim 1,wherein a gate voltage in a sub-threshold regime is applied at theelectrode.
 7. The method of claim 1, further comprising a membranecontaining the biomolecules immersed in the electrolyte.
 8. The methodof claim 1, further comprising an oxide layer configured to insulate adrain region of the sensor from the electrolyte, and an oxide layerconfigured to insulate a source region of the sensor from theelectrolyte.
 9. The method of claim 1, wherein the planar FET has athickness of less than about 10 nm, and a channel length that is aboutequal to a channel length of the silicon fin.
 10. The method of claim 1,wherein the silicon fin, a source region, and a drain region are locatedon a buried oxide layer, and wherein the sensor further comprises asilicon back gate located underneath the buried oxide layer on a side ofthe buried oxide layer opposite to the silicon fin, the source region,and the drain region.
 11. The method of claim 1, wherein the gatefurther comprises a silicon back gate that has a bias configured toadjust a threshold voltage of the sensor.
 12. The method of claim 1,wherein the silicon back gate is grounded.
 13. The method of claim 1,wherein the antibodies are located on an outer surface of the dielectricmaterial that comprises the gate dielectric.
 14. The method of claim 1,wherein the antibodies are in direct contact with the electrolyte.